Therapeutics - HIV Combined
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Therapeutics - HIV Combined
Therapeutics - HIV
Therapeutics - HIV
What type of drug is Emtricitabine-Emtriva?
What type of drug is Abacavir+Lamivudine - Epzicom?
What type of drug is Emtricitabine+Tenofovir DF – Truvada?
What type of drug is Lamivudine+Zidovudine – Combivir?
What type of drug is Nevirapine – Viramune?
What type of drug is Delavirine – Rescriptor?
What type of drug is Maraviroc?
CCR5 co-receptor antagonist (Fusion Inhibitor)
What are the Fusion inhibitors?
Maraviroc and Enfuvirtide
What is the generic name for Fuzeon?
What is the brand name for Enfuvirtide?
What is the brand name for Maraviroc?
What is the generic name for Selzentry?
What type of drug is Efavirenz – Sustiva?
What type of drug is Atripla (tenofovir + emtricitabine + efavirenz)?
What type of drug is Etravirine – Intelence?
What type of drug is Rilpivirine – Edurant?
What type of drug is Complera (tenofovir + emtricitabine +rilpivirine)?
Atazanavir has better or worse Bioavailability with food?
How is Atazanavir metabolized?
Metabolized by P4503A inhibitor/substrate
What are the SE for Atanazivir?
hyperbilirubinemia – (jaundice); HA; rash; GI symptoms; 1st degree A-V block; hyperglycemia; fat maldistribution
What is the preferred boosted-PI by DHHS guidelines?
Daranavir will be used along with ___________.
Daranavir should be given with or without food?
Daranavir can be used with what type of HIV virus?
Used for wild-type and PI-resistant virus
What are the SE of Daranavir?
Hepatitis; S-J syndrome; TEN; HA (15%); N (18%); diarrhea (20%)
Contains sulfa moiety – rash
How is Daranavir metabolized?
Fosamprevavir is effected by food in what way?
No food effect
What CYP interactions does Fosamprevavir have?
What are the SE of Fosamprevavir?
rash 19% S-J syndrome; headache; hyperlipid; fat maldistribution;
Sulfa moiety – rash
Indinavir has what CYP interaction?
Indinavir has what SE?
Nephrolithiasis (kidney stones); GI intol; hyperbilirubinemia; hyperlipid; hyperglycemia; fat maldistribution; headache; blurred vision; rash; red. PLTs
Lopinavir+Ritonavir should be taken with or without food?
Mod. Fat meal elevates AUC 48% and 80% (caps/solution)
What CYP effects does Lopinavir+Ritonavir have?
What SE does Lopinavir+Ritonavir have?
GI intol; hyperlipid; elevated LFTs; hyperglycemia; fat maldistribution
Nelfinavir should be taken with or without meals?
Concs. Increase 2-3 fold – take w/meals
Nelfinavir has what CYP effects?
Nelfinavir has what SE?
diarrhea; hyperlipid; hyperglycemia; fat maldistribution; elevated LFTs
Tipranavir is not recommended in what group and why
Not recommended in tx-naïve pts.
Use for People to fall back on if they develop resistance
What are the SE of Tipranavir?
GI effects – N, V, D
PIs have what effect on Azoles?
Increase Azole concentrations
PIs have what effect on Clarithromycin?
Increase Clarithromycin concentrations
PIs have what effect on PPIs?
Decrease PPI concentrations (may be equally effective though)
PIs have what effect on Opioids?
Increase opioid levels
PIs have what effect on antiarrhythmics?
Increase antiarrhythmic levels
PIs have what effect on anticonvulsants?
Reduce concentration of anticonvulsants and PI
What other drugs are CI with PIs?
What effect do PIs have on Warfarin?
What effect do PIs have on statins?
What are the Non-Nucleoside Reverse transcriptase inhibitors?
Nevirapine - Viramune
Delavirine - Rescriptor
Efavirenz – Sustiva
Atripla (tenofovir + emtricitabine + efavirenz)
Etravirine - Intelence
Rilpivirine – Edurant
Complera (tenofovir + emtricitabine +rilpivirine)
What is the brand name for Nevirapine?
What is the brand name for Delavirine ?
What is the brand name for Efavirenz?
What is the brand name for tenofovir + emtricitabine + efavirenz?
What is the brand name for Etravirine?
What is the brand name for Rilpivirine?
What is the brand name for tenofovir + emtricitabine +rilpivirine?
What is the generic name for Viramune?
What is the generic name for Rescriptor?
What is the generic name for Sustiva?
What is the generic name for Atripla?
Tenofovir + emtricitabine + efavirenz
What is the generic name for Intelence?
What is the generic name for Edurant?
What is the generic name for Complera?
Tenofovir + emtricitabine +rilpivirine
Delavirdine should be separated by 1 hr from what other drugs?
Didanosine or antacids
How is Delavirdine effected by food?
No food effect
How is Delavirdine metabolized?
By P4503A (inhibitor); 51% excreted in urine (as metabolites)
What are the SE of Delavirdine?
rash; elevated LFTs; headache
Use of DLV is not recommended due to:
High pill burden, dose frequency, SE and DDIs
Efavirenz has good or bad bioavailability?
How is Efavirenz metabolized?
By P4503A (mixed inducer/inhibitor)
What are the SE of Efavirenz?
Rash; CNS symptoms (52%) = Suicide ideation; elevated LFTs; false + cannabinoid test; teratogenic in monkeys (try not to use in 1st trimester)
Probably shouldn’t use with schizophrenia or depression
Is Efavirenz used as an initial therapy?
Nevirapine has good or bad bioavailability?
What is Nevirapine metabolized by?
What are the SE of Nevirapine?
Rash (37%); S-J syndrome; hepatitis; fatal hepatic necrosis particularly in women (pregnancy)
Entravirine has in vitro activity against what?
Entravirine should be taken with or without food?
CYP450 3A4 inducer
: rash 9%; S-J syndrome; nausea 13%
Is Entravirine used initially?
Not usually, usually just used in NNRTI-resistant strains
Rilpiverine is usually combined with what other drugs?
Tenofovir + emtricitabine
What group of patients is Rilpiverine usually used in?
Ttreatment naïve pts
VL < 100,000
What are the SE of Rilpiverine?
Depression (4%), insominia, headache (3%), and rash (3%)
What drug requires a viral oad of < 100,000?
Cross resistance to efavirenz, etravirine, and/or nevirapine is likely after development of resistance to _________.
Cross resistance ___________,___________ and/or ______________is likely after development of resistance to rilpivirine.
to efavirenz, etravirine, and/or nevirapine
NNRTIs have what effect on Azole antifungals?
Decrease in Azole conc.
Increase in NNRTI conc.
What NNRTIs affects Clarithromycin and what effect do they have?
Increase in both Clarithromycin and NNTRI concentration
What NNRTIs affects PPIs and what effect do they have?
Decrease PPI levels (CI)
What NNRTIs affects Opioids and what effect do they have?
Decrease Opioid levels
Anticonvulsants are CI with what NNRTIs?
Rifampin/Rifabutin are CI with what NNRTIs?
Benzodiazapines are CI with what NNRTIs?
What NNRTIs affects Warfarin and what effect do they have?
Increase Warfarin levels
Enfuvirtide is used at what point in treatment?
Usually all other treatments exhausted
Low CD4 cells
How is Enfuvirtide used for the treatment of HIV-1?
In combination with other antiretroviral agents in treatment-experienced patients despite ongoing antiretroviral therapy
What is the MOA of Enfuvirtide?
Interferes with the entry of HIV-1 into cells by inhibiting fusion of viral and cellular membranes
Maraviroc is a CCR5 co-receptor antagonist, what is the MOA of this drug class?
What is Maraviroc indicated for?
Combination antiretroviral treatment in adults
Only for CCR5-tropic HIV-1 detectable disease
Test to determine if you have CCR5-tropic virus
For use in patients who have evidence of viral replication
HIV-1 strains resistant to other antiretroviral agents
What is the MOA of Maraviroc?
Binds to human CCR5 on cell membrane
Prevents interaction between HIV-1 gp120 and CCR5
Blocks entry of HIV-1 into human cells
23% FF* - 100 mg dose; 33% FF* - 300 mg dose
What are the side effects of Maraviroc?
Abdominal pain, cough, dizziness, rash, hepatotoxicity, orthostatic hypotension
Should you take a lower or higher dose if you give Maraviroc with a strong CYP3A inhibitor?
Should you take a lower or higher dose if you give Maraviroc with a NRTIs, tipranavir/ritonavir, Nevirapine, Enfuvirtide?
Should you take a lower or higher dose if you give Maraviroc with given with CYP3A inducers (efavirenz, rifampin, etc.)?
What is the bioavailability of Maraviroc associated with?
What are the integrase inhibitors?
Raltegravir – Isentress
Dolutegravir – Tivicay
Dolutegravir abacavir/lamivudine - Triumeq
Elvitegravir – Stribild (quad pill)
Cobicistat – Tybost
Elvitegravir – Vitekta
What is the brand name for Raltegravir?
What is the brand name for Dolutegravir?
What is the brand name for Dolutegravir abacavir/lamivudine?
What is the brand name for Elvitegravir?
Stribild (quad pill)
What is the brand name for Cobicistat?
What is the brand name for Elvitegravir?
What is the generic name for Isentress ?
What is the generic name for Tivicay?
What is the generic name for Triumeq?
What is the generic name for Stribild (quad pill)?
What is the generic name for Tybost ?
What is the generic name for Vitekta?
What is the MOA of Raltegravir?
Integrase inhibitor – prevent insertion of HIV DNA into the human DNA genome
Block the formation of HIV-1 provirus
What group of patients is Raltegravir used in?
Treatment of HIV for tx-naïve and drug resistant pts with HAART
Should Raltegravir be administered without regard to food?
How long does it take to reach steady-state after beginning Raltegravir?
Achieved within 2 days of dosing
How is Raltegravir metabolized?
By UGT1A1 via glucuronidation
What are the side effects of Raltegravir?
Skin rash evolve to Stevens-Johnsons syndrome
What is the dose of Dolutegravir (Tivicay)?
50 mg QD
Take BID if using enzyme inducers like
: efavirenz, boosted fosamprenavir, tipranavir, or rifampin
Treatment-experienced patient – 50 mg BID
Should you give Dolutegravir (Tivicay) with or without food?
Can be administered without regard to food
What should patients on Dolutegravir (Tivicay) avoid?
Avoid cation containing meds
: mg, Ca supplements, iron, sucralfate, antacids
: phenytoin, phenobarbital, carbamazepine,
What are the Side effects of Dolutegravir (Tivicay)?
Hypersensitivity reactions (rash)
Worsening or elevated LFTs
What does Stribild contain?
Tenofovir, emtricitabine – NRTIs
Elvitegravir – integrase inhibitor
Cobicistat – novel P450 inhibitor (no activity against HIV)
What patients are eligible to receive Stribild (Tenofovir, emtricitabine, Eltegravir and Cobicistat)?
Used for tx-naïve patients
Only in patients with CrCl > 70 ml/min
What is the dose of Stribild (Tenofovir, emtricitabine, Eltegravir and Cobicistat)?
1 tab QD
Cobicistat is FDA approved to be given with what other drugs?
FDA approved to be given with atazanavir or darunavir
What type of drug is Cobicistat?
Elvitegravir comes in what dosage sizes?
85 & 150 mg tablets
How is Elvitegravir used?
With boosted PI + another drug (NRTI)
What is the most common side effect of Elvitegravir?
What is EC90?
Concentration of drug that are needed to inhibit 90% of the viral growth
A resistant virus EC90 compared to a wild-type virus is many times lower or higher?
Phenotypic resistance is the consequence of____________________________________.
Specific mutations in target genes
Combination regimens with enhanced antiviral potency suggests that the emergence of resistance is reduced when____________________________.
viral replication is effectively suppressed
What is the most common reason for resistance to develop to HIV drugs?
(Make regimens doable)
What is “Viral load”?
Number of RNA copies in the serum
Indirect reflection of the number productively infected cells
associated with the rate of disease progression and time of death
HIV RNA viral load or CD4 counts are more predictive of disease progression?
RNA viral load
Typically ____________ virions are produced daily.
10^9 to 10^10
When What is HIV RNA assay used for?
Assessing baseline status in newly diagnosed
Assessing response to therapy
Assessing development of resistance to current therapy
What are the benefits of Combination therapy for HIV?
Reduced toxicity and emergence of resistance
The minimal change in viral load considered to be statistically significant is:
A threefold or 0.5 log copies/mL change
Optimal viral suppression is generally defied as a viral load below the level of detection, what is the level of detection?
< 200 copies/mL
How long does it take for an antiviral regimen to produce viral suppression?
Achieved in 12-24 weeks
Didanosine is not recommended as initial therapy due to:
What are the SE of Didanosine?
Pancreatitis (+ D4T); peripheral neuropathy; nausea; diarrhea;
lactic acidosis (rare but life threatening – NRTIs class effect)
What NTRIs can cause Lactic acidosis?
Is Emtricitabine used for initial therapy?
Does Emitricitabine effected by food consumption?
No food effect
Does Emtricitabine have poor or good Bioavailability?
What drugs should Emtricitabine not be used with?
Lamivudine (3TC) – Too similar
What are the SE of Emtricitabine?
Toxicity – minimal
HA, N/V, diarrhea – occasionally
Lactic acidosis with hepatic steatosis
Lamivudine has what bioavailability and T ½?
Bioavail = 86%
What is Lamivudine also used to treat?
What are the SE of Lamivudine?
Toxicity – lactic acidosis
When would you use Stavudine?
Not recommended by DHHS due to side effects
How is Stavudine excreted?
Renal excretion -50%
What are eth SE of Stavidine?
: lipodystrophy (highest incidence); hyperlipidemia; lactic acidosis
Do not use D4T + ddI together (CIPregnancy)
Is Tenofovir recommended for initial therapy?
How is Tenofovir excreted?
What are the SE of Tenofovir?
Toxicity: headache; N/V; diarrhea; renal insuff; lactic acidosis
Is Tenofovir used very much?
Zidovudine is metabolized how?
What are the SE of Zidovudine?
Toxicity: bone marrow suppression (CI Hgb < 8); GI intolerance; insomnia; lactic acidosis
Are protease inhibitors usually used alone?
No often boosted with Ritonavir
How are most PI metabolized?
When you give Ritonavir with PIs what activity are you using it for?
Inhibit metabolism of the PI (not used as an antiretroviral)
PI inhibitors should be taken with or without food?
With a moderate to high fat meal (eggs/bacon/sausage/gravy)
What are the protease inhibitors?
Indinavir - Crixivan
Nelfinavir - Viracept
Ritonavir – Norvir
Lopinavir/Ritonavir – Kaletra
Fosamprenavir - Lexiva
Atazanavir – Reyataz
Tipranavir – Aptivus
Darunavir – Prezista
What is the brand name for Indinavir?
What is the brand name for Nelfinavir ?
What is the brand name for Ritonavir?
What is the brand name for Lopinavir/Ritonavir?
What is the brand name for Fosamprenavir?
What is the brand name for Atazanavir?
What is the brand name for Tipranavir?
What is the brand name for Darunavir?
What is the generic name for Crixivan?
What is the generic name for Viracept?
What is the generic name for Norvir?
What is the generic name for Kaletra?
What is the generic name for Lexiva?
What is the generic name for Reyataz?
What is the generic name for Aptivus?
What is the generic name for Prezista?
What type of drug is Indinavir – Crixivan?
What type of drug is Nelfinavir - Viracept?
What type of drug is Raltegravir – Isentress ?
What type of drug is Dolutegravir – Tivicay?
What type of drug is Dolutegravir abacavir/lamivudine – Triumeq?
What type of drug is Elvitegravir – Stribild (quad pill)?
What type of drug is Cobicistat – Tybost ?
Integrase inhibitor/Enzyme inhibitor for p450 system ?
What type of drug is Elvitegravir – Vitekta?
What type of drug is Ritonavir – Norvir?
What type of drug is Lopinavir/Ritonavir – Kaletra?
What type of drug is Fosamprenavir - Lexiva?
What type of drug is Atazanavir – Reyataz?
What type of drug is Tipranavir – Aptivus?
What type of drug is Darunavir – Prezista?
What type of drug is Zidovudine – Retrovir?
What type of drug is Didanosine - Videx?
What type of drug is Lamivudine - Epivir?
What type of drug is Stavudine - Zerit?
What type of drug is Abacavir - Ziagen?
What type of drug is Tenofovir-Viread?
What can be used for prophylaxis for heterosexual transmission of HIV-1?
1% tenofovir gel
What is used for prophylaxis for MSM transmission of HIV-1?
Most opportunistic infections occur when CD4+ cells have fallen to what level?
How is acute Pneumocystis jerovici pneumonia (PCP) (Protozoal infection of the lungs) treated in AIDS?
: TMP-SMZ for 21 days (DOC)
: Pentamidine if rash develops with Bactrim
Prophylaxis - TMP-SMZ 1 DS or SS qd for life
What is the MOA of Bactrim?
: Inhibits dihydrofolate formation from PABA, thus interfering with bacterial folic acid synthesis and growth
: inhibits dihydrofolate reduction to tetrahydrofolate
What is the Spectrum for Bactrim?
: MSSA, MRSA, Strep, Listeria
: Enterobacteriaceae, E. coli, H. influenzae, Stenotrophomonas
Does not cover
: Pneumocystis jiroveci, Nocardia, Toxoplasma, Legionella
Toxoplasmic encephalitis is a Protozoan parasite that usually invades CNS in AIDS patients, what is the treatment?
Pyrimethamine QD + sulfadiazine QID for 6-12 weeks
clindamycin + pyrimethamine
How do you prophylax for Toxoplasmic encephalitis?
: PCP prophylaxis with Bactrim
: dapsone + pyrimethamine
How do you treat TB in HIV patients?
Isoniazid + pyridoxine QD x 12 months
What is the Prophylaxis regimen for M. avis (MAC)?
: clarithromycin BID or azithromycin Qw
Clarithro has P450 DDIs, so go for Azithro first
What is the Candidiasis prophylaxis regimen?
Cryptosporidiosis is a Protozoan parasite that causes mild to intractable diarrhea in AIDS patients, how is it managed?
Nitazoxanide FDA approved
octreotide (Sandostatin) may control severe diarrhea
What is the Histoplasmosis Prophylaxis regimen?
must have an acid environment to absorbed this drug (Diet soda)
Posaconazole – alternative option
Must take with food for absorption
How do you treat Cytomegalovirus (CMV) in HIV?
Ganciclovir or foscarnet
Cidofovir – hard on kidneys so try to avoid
HSV is treated with what drug in HIV?
What are the risk factors for HIV?
IV drug use/abuse
sex partners in abuse groups
heterosexual men and women
Infants of above groups
What are the Symptoms of HIV?
What labs indicate HIV?
CBC - decrease in WBC; decrease in H/H; decrease in platelets (slight)
T-cells subsets - prognostic valve (indirect)
T-helper (CD4) count (<500)
Skin-test anergy (can’t mount an immune response if they get a skin test of some sort)
ELISA IgM or ELISA/Ag (Quick screening test)
Western blot – if negative - perform HIV viral load
What drug is used to prevent HIV infection in high risk individuals?
How do you prevent an HIV infection after an errant needle stick?
Decide whether to get treatment
Treatment (prophylaxis) - start ASAP (within 2 h)
Lasts 6 months if ELSIAs are all negative
ELISA - 0, 6 wks, 3 & 6 months
What are the Nucleoside reverse transcriptase inhibitors?
Zidovudine - Retrovir
Didanosine - Videx
Lamivudine - Epivir
Stavudine - Zerit
Abacavir - Ziagen
Abacavir+Lamivudine - Epzicom
Emtricitabine+Tenofovir DF – Truvada
Lamivudine+Zidovudine – Combivir
What is the brand name for Zidovudine?
What is the brand name for Lamivudine?
What is the brand name for Stavudine?
What is the brand name for Tenofovir?
What is the brand name for Abacavir?
What is the brand name for Didanosine?
What is the brand name for Emtricitabine?
What is the brand name for Abacavir+Lamivudine?
What is the brand name for Emtricitabine+Tenofovir DF?
What is the brand name for Lamivudine+Zidovudine?
Nuceoside reverse transcriptase inhibitors need what to happen before they are active?
Phosphorylation process (tri or di phosphorylation)
What is the MOA of Nucleoside Reverse Transcriptase inhibitors?
Similar to Purines and Pyrimidines
Integrated in replication chain
Stop reverse transcriptase from replicating the DNA strand
Prevent formation of new virions
What is the generic name for Retrovir?
What is the generic name for Epivir?
What is the generic name for Zerit?
What is the generic name for Ziagen?
What is the generic name for Viread?
What is the generic name for Videx?
What is the generic name for Emtriva?
What is the generic name for Epzicom?
What is the generic name for Truvada?
What is the generic name for Combivir?
How often is Abacavir (ABC) given?
BID or QD
What is Abacavir metabolized by?
EtOH leads to elevated ABC
What are the major risks of taking Abacavir?
Potentially fatal hypersensitivity reactions (Fever/Rash/N/V, Anorexia, SOB, cough, sore throat)
How can you avoid Hypersensitivity reactions associated with Abacavir?
Screen for HLA B*5701
Homozygous + or Heterozygous + are likely to have a hypersensitivity rxn
100% positive predictive value for the rxn
What combination therapy should be avoided with Abacavir?